The lysis of allogeneic cells by thymus-derived lymphocytes (T cells) from alloimmunized donors is a widely documented, but poorly understood, phenomenon. The proposed studies will examine several aspects of T cell-mediated lysis in a manner which, it is felt, will provide mechanistic insight into the lytic process. The lysis of 51Cr-labelled DBA/2 mastocytoma cells (p815) by lymphocytes from alloimmunized C57BL/6 mice will primarily serve as the assay system. Lysis in this system is reversibly inhibited by cytochalasin B, by prostaglandins E1 and E2 and by EDTA. Additionally, colchicine inhibits cytolysis in an irreversible manner. Because of the specificity of these inhibitors in other cell systems, T cell-mediated cytolysis may be dependent on the secretion of a soluble mediator, lymphotoxin (LT). This hypothesis will be tested by assessing the effects of a monospecific anti-LT serum on T cell-mediated cytolysis. Additionally, the role of the T cell's antigen receptor in cytotoxic expression will be evaluated. Specifically, two killer cell populations will be mixed, and following coculture, the effects on the cytolytic activity of both populations will be reassessed. Of particlar interest will be the results of such mixing experiments when antigen recognition can proceed in only one direction (e.g., a anti b mixed with b anti d). In this manner evidence will be sought for direct linkage between antigen binding and lytic expression. BIBLIOGRAPHIC REFERENCES: Bubbers, J.E. and Henney, C.S., Studies on the Synthetic Capacity and Antigenic Expression of Glutaraldehyde Fixed Target Cells, J. Immunol. 114:1126, 1975. Plaut, M., Lichtenstein, L.M. and Henney, C.S., Properties of a Subpopulation of T Cells Bearing Histamine Receptors. J. Clin. Invest. 55:856, 1975.